The objectives of this proposal are to clarify the neuroendocrine control mechanisms for growth hormone, prolactin and thyrotropin releasing hormone using an integrated approach involving measurement of the hypothalamic releasing and inhibiting factors under basal conditions and in response to perturbations of the respective hypothalamic pituitary axis. Bioassays for the releasing and inhibiting activities for each pituitary hormone have been established and alterations in their levels in hypothalamic tissue and their release in response to specific stimuli are in progress. A study of the biosynthesis of specific hypothalamic hormones is being conducted in normal and neoplastic tissue and evidence for heterogeneity of releasing factors in different anatomic regions is being sought. A search for releasing and inhibiting factors in neoplastic tissue is in progress and characterization of a growth hormone-releasing factor isolated from extra-pituitary tumors associated with growth hormone hypersecretion is being performed.